Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sex steroids exert potent effects on mood and mental state in the human. Our previous experimental findings in female rats suggest that these effects may be mediated, in part, by the action of estrogen on the 5-hydroxytryptamine2A receptor (5-HT(2A)R) and serotonin transporter (SERT) in brain. Here we review our recent findings on the effect of acute (approximately 32 h) testosterone manipulation on central 5-HT(2A)R and SERT in male rats. Castration decreased while testosterone or estrogen, but not 5alpha-dihydrotestosterone (5alpha-DHT), increased significantly the content of 5-HT(2A)R mRNA and SERT mRNA in the dorsal raphe nucleus (DR) and the density of 5-HT(2A)R and SERT binding sites in higher centers of the brain. The lack of effect of 5alpha-DHT, a potent androgen which cannot be converted to estrogen, suggests that the action of testosterone depends upon its conversion to estrogen by aromatase. This may also explain why estrogen, but not testosterone or 5alpha-DHT, increased the density of 5-HT(2A)R binding sites in the caudate-putamen, a brain region where aromatase is scarce. The estrogen induction of SERT mRNA is most prominent in the rostral DR and this together with the correlation between sensitivity of DR serotonin neurons to estrogen and neurotoxic amphetamine derivatives provides a potential topochemical handle with which to investigate testosterone/estrogen regulation of SERT gene expression. These findings are discussed in relation to the possible role of interactions between sex steroids and serotonin mechanisms in mood disorders, schizophrenia and Alzheimer's disease.
 ...
PMID:Androgen actions on central serotonin neurotransmission: relevance for mood, mental state and memory. 1055 90

The serotonin transporter gene (SERT) plays an important role in the serotonin uptake into neurons. Recently, several polymorphisms including a variable-number-tandem-repeat (VNTR) in the second intron and an insertion/deletion polymorphism (5-HTT linked polymorphic region, 5-HTTLPR) were identified and reported to be associated with a variety of mental illnesses, including major depression, bipolar disorder, anxiety-related traits, and autism. In our study, we performed an association study between the SERT VNTR polymorphism and schizophrenia (n = 260), bipolar disorder (n = 137), and unipolar depression (n = 33) in the Han Chinese. A large group of ethnically matched control individuals (n = 362) were also genotyped. Allele 12 of the VNTR polymorphism was associated with schizophrenia (P = 0.007) and unipolar depression (P = 0.011). Bipolar disorder was not associated with the VNTR (P = 0.93). Thus, we conclude that the SERT VNTR polymorphism may be a risk factor for both schizophrenia and unipolar depression, but not for bipolar disorder, in the Han Chinese.
 ...
PMID:Tentative association of the serotonin transporter with schizophrenia and unipolar depression but not with bipolar disorder in Han Chinese. 1078 Feb 68

A variable number tandem repeat (VNTR) polymorphism consisting of multiple copies of a 17-bp repeat in the second intron of the serotonin transporter gene (SERT) has been reported. Different alleles of this VNTR have been found to be associated with bipolar disorder and schizophrenia. These findings have been confirmed in some populations, but disconfirmed in others. Furthermore, significant ethnic variations in the distribution of these alleles both in normal and patient populations also have been reported. We analyzed the VNTR polymorphism in 50 Indian patients with bipolar disorder and in ethnically matched controls. Two alleles corresponding to 10 and 12 repeats of the VNTR were found in both groups. There were no significant differences either in allele frequency or genotype frequency between the two groups. The nine-repeat allele that has been reported in Japanese and Caucasian populations was absent in our sample. Although it will be important to extend the present study in a larger sample, our initial results do not suggest any large association with alleles of the VNTR in the SERT gene and bipolar disorder in Indian patients. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:170-172, 2000.
 ...
PMID:Association analysis of 5HT transporter gene in bipolar disorder in the Indian population. 1089 91

Serotonin is implicated in the pathogenesis of schizophrenia. Following serotonin release, the serotonin transporter (5-HTT) is the major determinant of serotonin inactivation. The present study tested the hypothesis that a biallelic polymorphism in the 5' regulatory region of the 5-HTT gene (5-HTTLPR) confers susceptibility to schizophrenia, association with the clinical manifestations of schizophrenia or clozapine response. 90 treatment-resistant schizophrenic patients were assessed using the Brief Psychiatric Rating Scale before and after clozapine treatment. The results demonstrated that the 5-HTTLPR variants did not play a major role in the susceptibility, clinical manifestations or clozapine response in schizophrenia.
 ...
PMID:Association study of a functional serotonin transporter gene polymorphism with schizophrenia, psychopathology and clozapine response. 1096 19

Neuroleptics are the mainstay of treatment for schizophrenia, but one of the complications is the development of tardive dyskinesia (TD). The pathophysiology of TD may involve dopamine-serotonin interaction. The serotonin transporter participates in the reuptake and termination of serotonin neurotransmission, and the gene that codes for this protein is thus a candidate gene for the development of TD. There is a functional polymorphism in the transcriptional control region of the serotonin transporter gene, and we investigated the association between this polymorphism and TD in Chinese schizophrenic patients. The patients who did not differ in age and sex distribution did not show variation on the rates of TD and Abnormal Involuntary Movements Scale (AIMS) scores with genotypes. Our findings suggest that 5-HTTLPR polymorphism is not a risk factor for TD in Chinese. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:712-715, 2000.
 ...
PMID:Tardive dyskinesia is not associated with the serotonin gene polymorphism (5-HTTLPR) in Chinese. 1112 Nov 66

Bipolar affective disorder is a highly heritable condition, as demonstrated in twin, family, and adoption studies. Morbid risk in first degree relatives is four to six times higher than the population prevalence of about 1%. However, the mode of inheritance is complex, and linkage findings have been difficult to replicate. Despite these limitations, consistent linkage findings have emerged on several chromosomes, notably 18p, 18q, 21q, 12q, 4p, and Xq. Two additional areas, 10p and 13q, have shown linkage in regions that appear to overlap with significant linkage findings in schizophrenia. Separate linkage studies in schizophrenia also have targeted the replicated bipolar linkages on 18p and 22q. New methods are being developed for fine mapping and candidate identification. Recent candidate gene studies include some positive results for the serotonin transporter gene on 17q and the catechol-o-methyltransferase gene on 22q. No other candidate gene studies are yet showing replicated results. A convincing demonstration for a susceptibility gene will probably require a mixture of case- control studies, family-based association methods, and pathophysiologic studies.
 ...
PMID:Genetics of bipolar affective disorder. 1112 48

Abnormalities of serotonin synthesis and metabolism may be associated with suicidality. The serotonin transporter gene (5-HTT) is one of the important genes involved in the regulation of serotonin neurotransmission. We examined the association of suicidal behavior in Chinese schizophrenic patients with a functional polymorphism of the promoter region of the 5-HTT gene (5-HTTLPR). The 5-HTTLPR genotype was determined by polymerase chain reaction for 76 suicidal and 262 non-suicidal patients with a diagnosis of schizophrenia (DSM-IV criteria). All subjects were unrelated to each other, and all were Chinese. There was no significant genotypic or allelic association of the 5-HTTLPR polymorphism with history of attempted suicide. From our results, this 5-HTTLPR polymorphism is unlikely to have a major effect on suicidal behavior in Chinese patients with schizophrenia.
 ...
PMID:Attempted suicide and polymorphism of the serotonin transporter gene in Chinese patients with schizophrenia. 1116 82

Associations of the VNTR-17 and 5-HTTLPR polymorphisms of the serotonin transporter gene with affective disorders, including depression, have been found. These polymorphisms were analyzed in two groups of Russian probands: patients with endogenous psychoses and control individuals without mental disorders (423 and 277 persons, respectively). No associations were found between VNTR-17 genotypes or alleles and the diseases. However, the frequency of 10/10 (VNTR-17) homozygotes increased with age in both patients and healthy persons. The results of the analysis of the 5-HTTLPR polymorphism suggest an association of the short (s) allele of the 5-HTTLPR polymorphism with schizophrenia and schizoaffective psychoses, but not with affective disorders.
 ...
PMID:[Polymorphism in the human serotonin transporter gene in endogenous psychoses]. 1119 Apr 80

Serotonergic pathways have been implicated in impulsive and aggressive behavior. Polymorphisms in the regulatory region of the serotonin transporter (5-HTT), in intron 7 of the tryptophan hydroxylase (TPH) gene and in the MAOA gene were previously reported to be associated with mood and anxiety disorders, impulsivity and aggression. In this study, we analyzed these polymorphisms in men and women with schizophrenia or schizoaffective disorder (n = 84) who met our criteria for violence (history of two or more assaults on others) or nonviolence (no history of either assaultive or threatening behavior). In males, a modest association between TPH genotype and history of violence (chi-square test = 6.703, degrees of freedom = 2, P = 0.035) was not statistically significant after correction for multiple comparisons (corrected P = 0.21). The TPH L allele was more frequent in violent males (chi-square = 5.323, degrees of freedom = 1, P = 0.021) but this difference also failed to withstand correction (corrected P = 0.126). No significant associations were found for either the 5-HTT or MAOA polymorphisms in males or females. These results tend to support previous reports by New et al. (1996; 1998) of an association between the TPH L allele and impulsive aggression in males with personality disorder, but larger studies are needed.
 ...
PMID:An association between a polymorphism of the tryptophan hydroxylase gene and aggression in schizophrenia and schizoaffective disorder. 1120 46

The human serotonin transporter gene (5-HTT) demonstrates two polymorphisms with possible functional impact: a 44-bp insertion/deletion polymorphism of the promoter region and a 17-bp variable number of tandem repeat polymorphism (VNTR) in intron 2 (STin2). Such genetic polymorphisms in the serotoninergic system may increase the susceptibility to schizophrenia or may serve as predictors of therapeutic response. We therefore analyzed these polymorphisms as susceptibility factors for schizophrenia by comparison of 684 schizophrenic inpatients with 587 healthy controls. We furthermore compared the therapeutic outcome of schizophrenic patients differentiated by the 5-HTT genotypes. Schizo-affective patients were more frequently homozygous for the 44-bp insertion allele (Odds ratio, OR: 1.6, 95% confidence interval, CI: 1.1--2.3, P < 0.03) than were all other schizophrenic patients and controls. The 17-bp VNTR alleles found were: STin2.7, 9, 10, and 12. Sequence analysis revealed seven different sequence motifs with an invariable arrangement. Patients with schizo-paranoid schizophrenia were more frequently homozygous for the STin2.12 allele than were controls (OR: 1.4, CI: 1.1--1.8, P < 0.007) and all other schizophrenic patients (OR: 1.6, CI: 1.2--2.3). The STin2.9 allele represented a risk factor for the residual subtype of schizophrenia (OR: 6.4, CI: 2.5--16.2, P < 0.001). On the basis of global clinical impressions, as well as measurements with the positive and negative syndrome scale we found no association of the polymorphisms with therapeutic response. In conclusion, the 44-bp polymorphism may be associated with the schizo-affective and the 17-bp VNTR with the residual and schizo-paranoid subtype of schizophrenia, findings which require further biochemical and epidemiological confirmation.
 ...
PMID:Serotonin transporter polymorphisms: no association with response to antipsychotic treatment, but associations with the schizoparanoid and residual subtypes of schizophrenia. 1131 20


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>